Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (211At)

Echigo, Hiroaki; Mishiro, Kenji; Munekane, Masayuki; Fuchigami, Takeshi; Washiyama, Kohshin; Takahashi, Kazuhiro; Kitamura, Yoji; Wakabayashi, Hiroshi; Kinuya, Seigo; Ogawa, Kazuma

doi:10.1007/s00259-023-06457-0

Cited by 11 publications

(4 citation statements)

References 39 publications

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“…9 e). Ga-DOTA-K([ 211 At]APBA)-c(RGDfK) with ABM delayed blood clearance, increased tumor accumulation compared to compounds without ABM, and showed strong therapeutic effects in tumor-bearing mice [ 93 ]. Clinical applications of TAT using RGD peptides are expected in the future.…”

Section: Radiolabeled Rgd Peptides With High Affinity For α ...mentioning

confidence: 99%

“…4-(4-Astatophenyl)butyric acid (APBA), in which the iodine in 4-(4-iodophenyl)butyric acid is replaced with astatine, also functions as an ABM, as described in the RGD peptide section [ 93 ]. Although only a few reports are present on 211 At-labeled compounds containing ABM owing to the short half-life of 211 At, APBA can be applied to other probes with different targeting moieties, which may facilitate the development of 211 At-labeled compounds containing ABM.…”

Section: Radiolabeled Compounds With Albumin-binding Moiety (Abm) For...mentioning

confidence: 99%

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Recent advances in the development of 225Ac- and 211At-labeled radioligands for radiotheranostics

Munekane,

Fuchigami,

Ogawa

2024

ANAL. SCI.

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Radiotheranostics utilizes a set of radioligands incorporating diagnostic or therapeutic radionuclides to achieve both diagnosis and therapy. Imaging probes using diagnostic radionuclides have been used for systemic cancer imaging. Integration of therapeutic radionuclides into the imaging probes serves as potent agents for radionuclide therapy. Among them, targeted alpha therapy (TAT) is a promising next-generation cancer therapy. The α-particles emitted by the radioligands used in TAT result in a high linear energy transfer over a short range, inducing substantial damage to nearby cells surrounding the binding site. Therefore, the key to successful cancer treatment with minimal side effects by TAT depends on the selective delivery of radioligands to their targets. Recently, TAT agents targeting biomolecules highly expressed in various cancer cells, such as sodium/iodide symporter, norepinephrine transporter, somatostatin receptor, αvβ3 integrin, prostate-specific membrane antigen, fibroblast-activation protein, and human epidermal growth factor receptor 2 have been developed and have made remarkable progress toward clinical application. In this review, we focus on two radionuclides, 225Ac and 211At, which are expected to have a wide range of applications in TAT. We also introduce recent fundamental and clinical studies of radiopharmaceuticals labeled with these radionuclides. Graphical abstract

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Section: Radiolabeled Rgd Peptides With High Affinity For α ...mentioning

confidence: 99%

Section: Radiolabeled Compounds With Albumin-binding Moiety (Abm) For...mentioning

confidence: 99%

Recent advances in the development of 225Ac- and 211At-labeled radioligands for radiotheranostics

Munekane,

Fuchigami,

Ogawa

2024

ANAL. SCI.

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“…This has limited the development of 211 At-labeled PSMA derivatives using astatobenzene structure as the 211 At-labeling moiety. On the other hand, metabolically stabile cyclic peptides such as the RGD peptide labeled with 211 At using astatobenzene showed high in vivo stability (Echigo et al 2024 ; Ogawa et al 2021 ). These results suggest that deastatination is involved in enzyme recognition and that astatobenzene derivatives, which are less easily recognized by enzymes, are stable in vivo.…”

Section: Introductionmentioning

confidence: 99%

In vivo stable 211At-labeled prostate-specific membrane antigen-targeted tracer using a neopentyl glycol structure

Suzuki,

Kannaka,

Hirayama

et al. 2024

EJNMMI radiopharm. chem.

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Background Prostate cancer is a common cancer among men worldwide that has a very poor prognosis, especially when it progresses to metastatic castration-resistant prostate cancer (mCRPC). Therefore, novel therapeutic agents for mCRPC are urgently required. Because prostate-specific membrane antigen (PSMA) is overexpressed in mCRPC, targeted alpha therapy (TAT) for PSMA is a promising treatment for mCRPC. Astatine-211 (211At) is a versatile α-emitting radionuclide that can be produced using a cyclotron. Therefore, 211At-labeled PSMA compounds could be useful for TAT; however, 211At-labeled compounds are unstable against deastatination in vivo. In this study, to develop in vivo stable 211At-labeled PSMA derivatives, we designed and synthesized 211At-labeled PSMA derivatives using a neopentyl glycol (NpG) structure that can stably retain 211At in vivo. We also evaluated their biodistribution in normal and tumor-bearing mice. Results We designed and synthesized 211At-labeled PSMA derivatives containing two glutamic acid (Glu) linkers between the NpG structure and asymmetric urea (NpG-L-PSMA ((L-Glu)2 linker used) and NpG-D-PSMA ((D-Glu)2 linker used)). First, we evaluated the characteristics of 125I-labeled NpG derivatives because 125I was readily available. [125I]I-NpG-L-PSMA and [125I]I-NpG-D-PSMA showed low accumulation in the stomach and thyroid, indicating their high in vivo stability against deiodination. [125I]I-NpG-L-PSMA was excreted in urine as hydrophilic radiometabolites in addition to the intact form. Meanwhile, [125I]I-NpG-D-PSMA was excreted in urine in an intact form. In both cases, no radioactivity was observed in the free iodine fraction. [125I]I-NpG-D-PSMA showed higher tumor accumulation than [125I]I-NpG-L-PSMA. We then developed 211At-labeled PSMA using the NpG-D-PSMA structure. [211At]At-NpG-D-PSMA showed low accumulation in the stomach and thyroid in normal mice, indicating its high stability against deastatination in vivo. Moreover, [211At]At-NpG-D-PSMA showed high accumulation in tumor similar to that of [125I]I-NpG-D-PSMA. Conclusions [211At]At-NpG-D-PSMA showed high in vivo stability against deastatination and high tumor accumulation. [211At]At-NpG-D-PSMA should be considered as a potential new TAT for mCRPC.

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“…This study led to the initiation of a phase I/II clinical trial using 211 At-BC8-B10 by the FDA. Shyril O Steen et al conjugated 211 At to an anti-CD38 monoclonal antibody to develop an 211 At-CD38 therapy in a planned clinical trial [ 24 ]. Hiroaki Echigo et al developed probes for multiradionuclide radiotheranostics using RGD peptide Ga-DOTA-[ 211 At]c [RGDf(4-At)K] for clinical applications.…”

Section: Introductionmentioning

confidence: 99%

The Different Strategies for the Radiolabeling of [211At]-Astatinated Radiopharmaceuticals

Gao,

Li,

Yin

et al. 2024

Pharmaceutics

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Astatine-211 (211At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of 211At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for 211At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of 211At-labeled compounds. The preclinical and clinical applications of 211At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of 211At production and quality control methods, and the continued evaluation of 211At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of 211At-based targeted alpha therapy. With the growing interest and investment in this field, 211At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.

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Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (211At)

Cited by 11 publications

References 39 publications

Recent advances in the development of 225Ac- and 211At-labeled radioligands for radiotheranostics

Recent advances in the development of 225Ac- and 211At-labeled radioligands for radiotheranostics

In vivo stable 211At-labeled prostate-specific membrane antigen-targeted tracer using a neopentyl glycol structure

The Different Strategies for the Radiolabeling of [211At]-Astatinated Radiopharmaceuticals

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